1. Field of the Invention
The present invention relates to a novel indole derivative exhibiting pharmaceutical actions such as a positive inotropic action, an anti-arrhythmic action, and a vasodilation action, pharmaceutically acceptable salts thereof, and a heart affection therapeutic agent comprising as an active ingredient the indole derivative or the salt thereof.
2. Description of the Background Art
Congestive heart failure is a state of disease involving a reduction in the cardiac output due to functional abnormalities of heart, accompanied by incapability of ejecting a sufficient quantity of blood required for tissues to metabolize. Heart failures were recently described by J. N. Cohn as a syndrome caused by a cardiac function insufficiency which involves (i) an decrease in a kinetic tolerance capacity, (ii) frequent occurrence of ventricular arrhythmia, and (iii) disorders occurring during the aftercare (J. N. Cohn, Circulation, 78, 1099 (1988)).
Diuretics, vasodilators and cardiac stimulants such as digitalis are used for the improvement of these syndromes.
Digitalis compounds are currently used widely as a cardiac stimulant. Digoxin, one of digitalis compounds, has been confirmed to promote cardiac ejection fractions and to suppress acceleration of heart failures. Digoxin further exhibits an action of decreasing the heart rate. It exhibits a long sustained action, does not produce drug resistance, and can be orally administered. In spite of these significant advantages, the effective concentration in blood and the toxic dose of digoxin are very close each other. In addition, digoxin sometimes induces arrhythmia. Because of these drawbacks of digoxin, research and development of non-glycoside cardiac stimulants which can be administered orally is being strongly promoted more recently.
An object of the present invention is therefore to provide a compound exhibiting a positive inotropic action, an antiarrhythmic action, and a vasodilation action, and useful as a heart affection therapeutic agent.
In view of this situation the present inventors have synthesized a number of compounds and have undertaken screening of these compounds using the positive inotropic action, the anti-arrhythmic action, and the vasodilation action as indicators. As a result, the present inventors have found that novel indole derivatives represented by formula (1) described below and pharmaceutically acceptable salts thereof can satisfy the above object and useful as a drug for treating heart affections. These findings have led to the completion of the present invention.